New theories of schizophrenia present it as a disease of myelination. This project proposes to examine and quantify changes in oligodendrocytes and myelination in the cingulum bundle of schizophrenics. A deeper understanding of the pathophysiology of schizophrenia may lead to innovative treatments for this chronic disease. A second-order stereologic approach will be used to quantify changes in the spatial distribution of oligodendrocytes in the cingulum bundle of human schizophrenics, using postmortem materials. A mouse model genetically engineered to be missing MAG, a myelin-related protein, will be studied to quantify changes in prefrontal cortical pyramidal cells that may be affected by dysmyelination. Cell morphology, dendritic arborization, and myelination will be compared across mutant and wildtype mice. In addition, diffusion tensor imaging will be used to compare anisotropy between living schizophrenic patients and controls. The anisotropy data will be correlated with changes in metabolism observed by PET imaging and will also be compared across stages of the disease. The same data will allow tracing of the cingulum bundle in schizophrenics and controls to look for differences in fiber targeting.